Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells
Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells
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DOI：
10.1016/j.lfs.2010.02.017
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发表时间：
2010-04-24
期刊：
影响因子：
6.1
通讯作者：
Matsuo, Takashi
中科院分区：
文献类型：
--
作者：
Hirao, Kouji;Yumoto, Hiromichi;Matsuo, Takashi
目的：研究儿茶素能否抑制龋病相关细菌、链球菌或病原体相关分子模式(PAMPs)刺激的人牙髓成纤维细胞(HDPF)中促炎介质的表达。主要方法：用儿茶素处理链球菌或PAMP刺激的HDPF，用RT-PCR和ELISA法检测促炎介质的表达和产生。进一步，用免疫印迹和ELISA法检测Toll样受体(TLR)2配体激活的信号转导通路。关键发现：炎症牙髓中，尤其是HDPF中，促炎介质表达增加。我们最近报道，牙髓的先天免疫反应可能主要是由主要表达的TLR2信号引起的。儿茶素是绿茶中的多酚化合物，通过多种机制发挥保护和愈合作用，包括抗氧化和抗炎作用。然而，目前还没有关于儿茶素对牙髓影响的报道。在本研究中，我们证明了儿茶素、(-)-表儿茶素没食子酸酯(CG)和(-)-表儿茶素没食子酸酯(EGCG)可抑制链球菌或PAMP刺激的HDPF中IL-8或PGE(2)的上调表达。在TLR2配体刺激的HDPF中，细胞外信号调节激酶(ERK)1/2、p38、c-jun氨基末端激酶(SAP/JNK)、核因子-kappaB或儿茶素的特异性抑制剂显著降低促炎介质的水平，这些信号转导分子的磷酸化被儿茶素抑制。意义：这些发现提示儿茶素可能是一种有效的牙髓炎症抗炎调节剂。(C)2010 Elsevier Inc.保留所有权利。
Aims: In this study, we evaluated whether catechins could inhibit the expression of pro-inflammatory mediators induced by dental caries-related bacteria, Streptococci, or pathogen-associated molecular patterns (PAMPs) stimulation in human dental pulp fibroblasts (HDPF). We further determined the mechanisms of the anti-inflammatory activity of catechins.Main methods: Streptococci or PAMP-stimulated HDPF were treated with catechin, and then the expression and production of pro-inflammatory mediators were determined by RT-PCR and ELISA. Furthermore, the signal transduction pathways activated with toll-like receptor (TLR)2 ligand were assessed by Immunoblot and ELISA using blocking assay with specific inhibitors.Key findings: Increased expressions of pro-inflammatory mediators are found in inflamed dental pulp, especially in HDPF. We recently reported that dental pulpal innate immune responses may mainly result from the predominantly-expressed TLR2 signaling. Catechins, polyphenolic compounds in green tea, exert protective and healing effects through multiple mechanisms, including antioxidative and anti-inflammatory effects. However, there are no reports concerning the effects of catechins on dental pulp. In this study, we demonstrated that the up-regulated expressions of IL-8 or PGE(2) in Streptococci or PAMP-stimulated HDPF were inhibited by catechins, (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG). In TLR2 ligand-stimulated HDPF, specific inhibitors of extracellular signal regulated kinase (ERK)1/2, p38, c-jun NH2-terminal kinase (SAP/JNK), NF-kappa B or catechins markedly reduced the level of pro-inflammatory mediators and the phosphorylation of these signal transduction molecules was suppressed by catechins.Significance: These findings suggest that catechins might be useful therapeutically as an anti-inflammatory modulator of dental pulpal inflammation. (C) 2010 Elsevier Inc. All rights reserved.